The broad objectives of this research plan are: a. To understand the physiological roles and functional significance of the peptide hormone calcitonin; b. To probe the mechanisms by which several humoral agents (parathyroid hormone, calcitonin and prostaglandins) affect mineral metabolism in target tissues; and c. To extend studies on mineral ion homeostasis to nonpeptide factors, especially prostaglandins. Several approaches will be used. We shall develop improved assay methods for measuring calcitonin and parathyroid hormone (affinity chromatography, radioreceptor assays, radioimmunometric assays, radioimmunoassays and new biological assays). The control of parathyroid hormone and calcitonin synthesis and secretion will be studied in cell and organ culture systems. The mechanisms of action of bone resorption-stimulating factors will be studied in isolated bone cells, in bone in organ culture, and in whole animals. New physiological roles for calcitonin will be sought in nonmammalian vertebrates (fish), and as a developmental hormone in the fetus. Studies of the calcitonin-excess syndrome (medullary thyroid carcinoma) will include development of improved methods for the early diagnosis and treatment, examination of the genetic mechanisms underlying the familial form of the disease, and the etiology of APUD-amyloid. Lastly, we shall study animal and cell culture models which may help to explain the hypercalcemia that is often associated with neoplastic disease.